Supervisor: Prof. Huang

Reporter: Sixuan Meng

2015-08-24

Enatioselective and Enantiospecific Transiton-

Metal-Catalyzed Cross-Coupling Reactions of

Organometallic Reagent To Construct C-C bond

Sarash E. Reisman et al. Chem. Rev. ASAP

Content

• Introduction

• Enantioselective Transition-Metal-Catalyzed Alkyl Cross-

Coupling Reactions

Reactions of secondary Alkylmetallic Reagents

Reactions of secondary Alkyl Electrophiles

• Transition-Metal-Catalyzed Enantiocontrolled Allylic

Substitution

Enantioselective Allylic Substitution Reactions

2

Instroduction

• Transition-metal-catalyzed Cross-coupling Reaction

C−C bond forming reactions between an organic electrophile (typically

an organic halide or pseudohalide, which in this review includes alcohols,

amines, and their derivatives) and an organometallic reagent, mediated by

a transition-metal catalyst.

• Enantiospecific Cross-Coupling

chirality exchange reactions in which the stereochemistry of a chiral,

enantioenriched substrate defines the stereochemistry of the product.

3

• Enantioselective Cross-Coupling

Reactions in which there

is selective formation of

one enantiomer over the

other as defined by a chiral

metal catalyst.

4

Content

• Introduction

• Enantioselective Transition-Metal-Catalyzed Alkyl Cross-

Coupling Reactions

Reactions of secondary Alkylmetallic Reagents

Reactions of secondary Alkyl Electrophiles

• Transition-Metal-Catalyzed Enantiocontrolled Allylic

Substitution

Enantioselective Allylic Substitution Reactions

5

Enantioselective Transition-Metal-Catalyzed Alkyl Cross-Coupling

Reactions

• Reactions of secondary Alkylmetallic Reagents

In principle, fast equilibration between the two enantiomers of a sec-

alkylmetallic reagent or between two diastereomers of a chiral transition

metal complex could enable enantioselective cross-coupling through a

dynamic kinetic asymmetric transformation (DYKAT)

6

Organomagnesium Reagent

7

Kumada, M. et al. Tetrahedron Lett. 1974, 15, 3

Kumada, M. et al. Tetrahedron Lett. 1977, 18, 1389

Brunner, H. et al. J. Organomet. Chem. 1981, 209, C1

8

• Proposed catalytic cycle for the enantioselective coupling of

α-methylbenzyl Grignard reagents

9

10

• Coupling of disubstituted alkenes

11

12

• Coupling of α-Silyl Grignard Reagents

Kumada, M. et al.

J. Org. Chem.

1986, 51, 3772

Kumada, M. et al.

Tetrahedron Lett.

1981, 22, 137

Kumada, M. et al.

Tetrahedron Lett.

1983, 24, 807

Organozinc Reagent (Negishi-type)

13

Ito, Y. et al. Chem. Commun. 1989, 495

Reisman, S. E. et al. Tetrahedron 2014, 70, 3259

14

• Enantioconvergent alkyl-alkyl coupling

Fu, G. C. et al. J. Am. Chem. Soc. 2013, 135, 10946

Organoboron Reagents

15

• Dual catalysis approach to asymmetric cross-coupling

Molander, G. A. et al. Science 2014, 345, 433

16

Reactions of secondary Alkyl electrophiles

With Organomagnesium Reagent (Kumada-Corriu)

17 Fu, G. C. et al. J. Am. Chem. Soc. 2010, 132, 1264

18

With Organozinc Reagent (Negishi)

Fu, G. C. et al. J.

Am. Chem. Soc.

2005, 127, 4594

Fu, G. C. et al. J.

Am. Chem. Soc.

2005, 127, 10482

Alkylzinc

Reagent

19

Arylzinc Reagent

Fu, G. C. et al. J. Am. Chem. Soc. 2008, 130, 12645

20 Fu, G. C. et al. Angew. Chem. Int. Ed., 2009, 48, 154

21

Fu, G. C. et al. JACS.

2014, 136, 12161

With Organoboron Reagent (Suzuki-Miyaura)

22 Fu, G. C. et al. J. Am. Chem. Soc. 2008, 130, 6694

23

Examples of directing groups for enatioconvergent Suzuki-Miyaura coupling

24 Fu, G. C. et al. J. Am. Chem. Soc. 2010, 132, 11027

25 Fu, G. C. et al. J. Am. Chem. Soc. 2014, 136, 3788

Transition-Metal-Catalyzed Enantiocontrolled Allylic Substitution

26

General principles of allylic substitution with hard nucleophiles

Enantioselective Allylic Substitution Reactions

Organomagnesium Reagents

27

28

Seminal Example of Cu-Catalyzed Asymmetric Allylic Substitution with Alkyl

Van Koten, G. et al. Tetrahedron Lett. 1995, 36, 3059

29

30 Feringa, B. L. et al. J. Am. Chem. Soc. 2013,135, 2140

Cu-catalyzed allyl−allyl coupling

Organozinc Reagents

31

Seminal Enantioselective Cu-Catalyzed Substitution of Allylic Chlorides

Knochel, P. et al. Angew. Chem. Int. Ed. 1999, 38, 379

32

33

Organoboron Reagents

With Organomagnesium Reagents

With Organoboron Reagents

Organoboron Reagents

34 Oi, S. et al. Org. Lett. 2012, 14, 4502

35

Hayashi, T. et al.

Angew. Chem.

Int. Ed. 2011, 50,

8656

Summmary

36

1）the analogous asymmetric cross-coupling reactions

of tert-alkyl partners represent a largely undeveloped

area

2） provide entry to molecules with all-carbon

quaternary centers

3）few ligands have been shown to support a broad

substrate scope with high selectivity

37

Thank you ！

Sarash E. Reisman et al. Chem. Rev. ASAP